The functional heterogeneity of the macrophage population will be studied with respect to inducible or constitutive production of bioregulatory macromolecules which influence myelopoiesis and lymphopoiesis. "Helper" macrophage populations will be assayed for capacity to produce stimulatory factors involved in the proliferation of granulocyte-macrophage, erythroid and megakaryocytic progenitor cells and mitogen-dependent T and B cell responses. "Suppressor" macrophages will be assayed for production of prostaglandins, interferon, tumor necrosis factor and other activities of relevance to the anti-proliferative and anti-neoplastic role of macrophages. Biophysical separation and cloned macrophage cell lines will be used to facilitate characterization of functionally distinct macrophage subpopulations. Macrophage activating agents, including endotoxin and C. parvum, will be used to induce secretion of regulatory macromolecules in non-producer macrophage cell lines or macrophage subpopulations and biochemical characterization of these activities will be performed. Separate analysis of granulocyte macrophage regulatory interaction will be carried out with emphasis on the regulatory role of granulocyte derived lactoferrin and macrophage derived GM-CSF, endogenous pyrogen and prostaglandin E. Network analysis of regulatory interactions between macrophages and B and T lymphocytes, hemopoietic stem cells and progenitor cells will be carried out in order to define the central regulatory importance of macrophages in hemopoietic regulation and immune function. Finally, the effector function of macrophages in host defense against neoplasia will be studied from the standpoint of differential sensitivity of tumor target cells to suppressive factors produced by stimulated or activated macrophages.